Treatment of Cushing's Disease by o,p′DDD

Luton, J. P.; Mahoudeau, J; Bouchard, P.; Thieblot, P.; Hautecouverture, M.; Simon, Deborah; Laudat, M H; Touitou, Yvan; Bricaire, H

doi:10.1056/nejm197903013000903

Cited by 196 publications

(97 citation statements)

References 16 publications

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“…There is now evidence for the anti-proliferative and anti-secretory effects of mitotane in adrenocortical cancer (18,19,20), but there are no recent data on its long-term efficacy or safety in the treatment of CD. The largest study to date was published from our center in 1979 and included 62 patients treated with mitotane, of whom 24 also received pituitary irradiation (21). The aim of the current study was to analyze the efficacy and side effects of mitotane as a first-or second-line treatment in patients with CD in a single center.…”

Section: Introductionmentioning

confidence: 99%

Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

Baudry

Coste

Khalil

et al. 2012

European Journal of Endocrinology

168

118

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Context: Alternatives to transsphenoidal pituitary surgery may be required in Cushing's disease (CD) as a first-or second-line treatment. Mitotane is a potent anti-cortisolic drug but has been rarely investigated in the treatment of CD. Objective: Evaluation of the efficacy and tolerance of mitotane in CD patients. Design and setting: Retrospective analysis of 76 patients treated with mitotane from 219 patients diagnosed with CD between 1993 and 2009 in a single center. Main outcome measure: Remission was defined as normalization of 24-h urinary free cortisol (24-h-UFC). Results: Remission was achieved in 48 (72%) of the 67 long-term treated patients, after a median time of 6.7 (5.2-8.2) months. Mean plasma mitotane concentration at the time of remission was 10.5G8.9 mg/l, with a mean daily dose of 2.6G1.1 g. A negative linear relationship was observed between plasma mitotane concentration and 24-h-UFC (P!0.0001). Seventeen of 24 (71%) patients with durable remission subsequently experienced recurrence, after a median time of 13.2 (5.0-67.9) months. At the time of treatment discontinuation, ACTH concentration was statistically associated with a lower recurrence probability (hazard ratios 0.57 (0.32-1.00), PZ0.05). Intolerance leading to treatment discontinuation occurred in 19 patients (29%). A pituitary adenoma became identifiable during mitotane treatment in 12 (25%) of the 48 patients with initial negative pituitary imaging allowing subsequent transsphenoidal surgery. Conclusion: Mitotane is useful at different stages of CD. Mitotane dose adjustment based on plasma concentration monitoring and side effects could control hypercortisolism in the majority of CD patients.

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Section: Introductionmentioning

confidence: 99%

Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

Baudry

Coste

Khalil

et al. 2012

European Journal of Endocrinology

168

118

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“…It has been shown to inhibit cortisol production via inhibition of multiple steroidogenic enzymes and to be efficacious in the treatment of CD (Young et al 1973, Luton et al 1979. Mitotane has a slow onset of action and based on its lipophilic nature, it is stored in adipose tissue, ensuring a long half-life of 18-159 days (Nieman 2002).…”

Section: Inhibitors Of Adrenocortical Steroidogenesismentioning

confidence: 99%

“…up to 16 weeks, whereas long-term treatment resulted in biochemical remission in about 80% of patients, although these patients were also treated with radiotherapy (Verhelst et al 1991). Mitotane, at lower dosages, can be useful in the treatment of CD (Luton et al 1979, Schteingart et al 1980, Kamenicky et al 2011. Schteingart et al (1980) reported clinical and biochemical remission of CD in 80% of patients treated with mitotane and pituitary irradiation.…”

Section: R Van Der Pas Et Al: Developments In the Medical Treatment mentioning

confidence: 99%

“…Schteingart et al (1980) reported clinical and biochemical remission of CD in 80% of patients treated with mitotane and pituitary irradiation. Another study showed control of hypercortisolemia using mitotane monotherapy in 38/46 patients, whereas mitotane and pituitary irradiation combination therapy was successful in 100% of patients (Luton et al 1979). Mitotane has, however, multiple side effects, which may limit long-term use.…”

Section: R Van Der Pas Et Al: Developments In the Medical Treatment mentioning

confidence: 99%

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New developments in the medical treatment of Cushing's syndrome

Pas¹,

Herder²,

Hofland³

et al. 2012

Endocrine-Related Cancer

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Cushing's syndrome (CS) is a severe endocrine disorder characterized by chronic cortisol excess due to an ACTH-secreting pituitary adenoma, ectopic ACTH production, or a cortisol-producing adrenal neoplasia. Regardless of the underlying cause, untreated CS is associated with considerable morbidity and mortality. Surgery is the primary therapy for all causes of CS, but surgical failure and ineligibility of the patient to undergo surgery necessitate alternative treatment modalities. The role of medical therapy in CS has been limited because of lack of efficacy or intolerability. In recent years, however, new targets for medical therapy have been identified, both at the level of the pituitary gland (e.g. somatostatin, dopamine, and epidermal growth factor receptors) and the adrenal gland (ectopically expressed receptors in ACTH-independent macronodular adrenal hyperplasia). In this review, results of preclinical and clinical studies with drugs that exert their action through these molecular targets, as well as already established medical treatment options, will be discussed.

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“…However, the onset of its action is slow (weeks or months), and the adverse effects associated with mitotane therapy (mainly digestive and neurological) require careful monitoring of drug levels. This kind of therapy is routinely used in only a few centers (33), and is more useful for adrenocarcinoma treatment.…”

Section: Treatment and Managementmentioning

confidence: 99%

A rare case of Cushing syndrome by cyclic ectopic-ACTH

Farage

Costa²,

Godoy-Matos

2012

Arq Bras Endocrinol Metab

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SUMMARYACTH-dependent Cushing syndrome (CS) due to ectopic ACTH production is most times difficult to manage. The identification of the source of ACTH may take many years. Surgery or chemotherapy for the primary tumor is not always possible. Control of Cushing symptoms is many times achieved using medication, or bilateral adrenalectomy in refractory cases. This case presents a Brazilian male who showed severe hypertension, mood changes, muscle weakness, darkening of skin, and increased abdominal fat. An investigation for Cushing syndrome was carried out and, after a four-year follow-up, a carotid glomus tumor (chemodectoma) was confirmed, a rare ectopic ACTH-producing tumor. Besides, the patient presented cyclic Cushing syndrome that was exacerbated by diverticulitis episodes. This case presents interesting pitfalls on diagnosis and management of ACTH-dependent CS. This is the only report of a chemodectoma that produced ACTH in the literature. Arq Bras Endocrinol Metab. 2012;56(5):324-30 SUMÁRIO A síndrome de Cushing ACTH-dependente causada por produção ectópica de ACTH é, muitas vezes, difícil de diagnosticar e conduzir. A identificação da fonte produtora de ACTH pode demorar muitos anos. A cirurgia ou quimioterapia para o tumor primário nem sempre é possível, sendo o controle do hipercortisolismo alcançado com uso de fármacos ou adrenalectomia bilateral, nos casos refratários. Este caso apresenta um homem com hipertensão grave, mudança de humor, fraqueza proximal, escurecimento da pele e aumento de gordura abdominal. A investigação para síndrome de Cushing foi feita e, após quatro anos de acompanhamento, confirmou--se um tumor de glomus carotídeo (quemodectoma), causa rara de tumor secretor de ACTH. Nesse período, o paciente apresentou síndrome de Cushing cíclica, exacerbada por crises de diverticulite. O caso ilustra pontos importantes no diagnóstico, no acompanhamento e na condução da síndrome de Cushing ACTH-dependente, sendo este o único caso de tumor de glomus de carótida produzindo ACTH descrito na literatura médica. Arq Bras Endocrinol Metab. 2012;56(5):324-30

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Treatment of Cushing's Disease by o,p′DDD

Cited by 196 publications

References 16 publications

Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

New developments in the medical treatment of Cushing's syndrome

A rare case of Cushing syndrome by cyclic ectopic-ACTH

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